When our old Homo sapiens Our ancestors left Africa for Eurasia around 60,000 years ago. They met and mated with some of the other human species that inhabited their new, colder home. Among them were the now-extinct Denisovans, who endowed modern humans with genes that may have helped us adapt to cold weather while increasing our susceptibility to schizophrenia and other mental health disorders.
The tryst between humans and other archaic hominid species has left an indelible mark on the genomes of present-day people around the world, with a small percentage of our DNA directly inherited from Neanderthals and Denisovans. By examining the genetic makeup of 26 current populations and crossing them with the genomes of our extinct cousins, the authors of a new study have discovered one of the most widespread traces of Denisovan DNA in modern humans .
According to the researchers’ analysis, current populations in all regions except Africa contain a particular variant of a gene called SLC30A9, which seems to have been obtained as a result of mating with Denisovans in the distant past. The gene itself codes for a protein called ZnT9, which transports zinc across cell membranes.
The variant does not appear in the Neanderthal genome, thus excluding that species as the source of the gene. At the same time, researchers found that modern African genomes typically contain an older variant of SLC30A9 which predates the introduction of the Denisovan allele.
The geographic distribution of the Denisovan SLC30A9 gene variant.
Image credit: Jorge Garcia and Elena Bosch
Through genomic analysis, we noted that the observed genetic variant came from our interbreeding with archaic humans in the past, possibly the Denisovans, explained study author Ana Roca-Umbert in a statement. Apparently, the change was beneficial and proved to be a selective advantage for humans. Consequently, this variation of SLC30A9 The gene was selected and reached current populations, added co-author Jorge Garcia-Calleja.
To examine how the Denisovan variant affects physiology, the team introduced this DNA into human embryonic kidney cells, noting that it changed the amount of zinc that entered key cellular structures such as mitochondria and the endoplasmic reticulum. This, in turn, led to changes in mitochondrial metabolism, preventing zinc overload and resulting in an overall gain of function.
Based on this observation, the study authors suspect that the genetic variant inherited from the Denisovans could have helped the ancients Homo sapiens become better adapted to the cold. However, since zinc imbalances can cause neurological disorders, it is possible that the DNA acquired by our ancestors during their relationships with other human species may have also left a mark on our mental health.
Confirming this negative side effect, the study authors write that the widely distributed Denisovan variant is known to be associated with greater susceptibility to several neuropsychiatric disorders. These include illnesses such as schizophrenia, bipolar disorder, depression and anorexia nervosa.
Integrating their various findings into a theory regarding the introduction of the Denisovan SLC30A9 variant of the human genome, the researchers speculate that cold adaptation may have led to this selection event outside of Africa, while also impacting the predisposition to neuropsychiatric disorders in modern humans.
The study is published in the journal PLOS Genetics.
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